EXPRESSION OF MITOCHONDRIAL RIBOSOMAL PROTEINS IN YEAST

本提案的长期目标是了解 线粒体的过程以及如何调节这一过程 通过发育和生理刺激。 作为必要的步骤 为了实现这些目标，这些研究将审查 生物合成的线粒体复合物的双重遗传来源， 确定这种复合物的组分是否协调 表达。 S.酿酒厂就是这样一个 复杂. 核编码的线粒体基因的表达 核糖体蛋白将被检查，以确定它们的最终 稳态水平与这些核糖体成分平衡 编码在线粒体中。 的检查 核编码的生物合成的调控方面 线粒体核糖体蛋白需要探针 为了测量mRNA和蛋白质的表达， 干扰核糖体成分合成的条件。 为此，将纯化线粒体核糖体蛋白， 用这两种方法分离出相应的基因， 抗体的 将尝试在哺乳动物中过表达这些基因。 酵母细胞相对于其他核糖体组分。 如果稳定- 线粒体核糖体编码的mRNA水平 蛋白质或核糖体蛋白本身不能被 大大高于其他组件， 调节其表达以实现平衡的机制 表达将被确定。 线粒体在细胞代谢中起核心作用， 线粒体异常，并与许多 病理状况，包括某些甲状腺肿瘤， 甲状旁腺和垂体 最近的研究表明， 线粒体发育调节中的损伤 生物发生可导致严重的临床病症和死亡。 作为 这样线粒体生物发生及其调节可以是直接的， 导致许多疾病的因素。 的组合 基础研究，如本提案所述， 过去的临床研究已经成功地用于 疾病的治疗管理。 预计这一 组合将继续，并可能在未来使用， 探索治疗管理的方法， 线粒体肌病

The long range goals of this proposal are to understand the process of mitochondrial and how this process may be regulated by developmental and physiological stimuli. As a necessary step in achieving these goals these studies will examine the biosynthesis of a mitochondrial complex of duel genetic origin to determine if the components of such a complex are coordinately expressed. The mitochondrial ribosome of S. cerevisiae is such a complex. The expression of nuclear-encoded mitochondrial ribosomal proteins will be examined to determine how their final steady-state levels are balanced with those ribosomal components that are coded in the mitochondria. An examination of the regulatory aspects of the biosynthesis of nuclear-encoded mitochondrial ribosomal proteins requires that probes be available to measure the expressioin of both mRNA and protein under conditions that perturb the synthesis of ribosomal components. To this end, mitochondrial ribosomal proteins will be purified and used both to isolate their corresponding genes and raise antibodies. Attempts will be made to overexpress these genes in yeast cells relative to other ribosomal components. If the steady- state levels of either mRNA coding for mitochondrial ribosomal proteins or the ribosomal proteins themselves cannot be substantially increased above that of other components, the mechanisms that regulate their expression to achieve balanced expression will be determined. Mitochondria play a central role in cellular metabolism and mitochondrial abnormalities and have been associated with many pathological conditions including certain neoplasms of the thyroid, parathyroid, and pituitary. More recent findings have suggested that lesions in the developmental regulation of mitochondrial biogenesis can lead to severe clinical disorders and death. As such, mitochondrial biogenesis and its regulation may be direct or contributing factors to many disease states. The combination of basic research such as that described within this proposal and clinical studies have been successfully used in the past for the therapeutic managements of diseases. It is anticipated that this combination will continue and may be used in the future to explore approaches to the therapeutic management of mitochondrial myopathies.